Overcoming checkpoint inhibitor (CPI) resistance has been a major area of investigation since the first PD-1 inhibitor was approved in 2014
Other than melanoma, PD-(L)1 re-challenge approaches have failed to show substantial benefit in randomized trials
Segmenting patients by resistance type may be a strategy for success, but only one of the pending Ph3 rechallenge trials in NSCLC is using this to select patients
Importantly, for any drug targeting the post-CPI setting, control arms of these failed trials hint that efficacy may be higher in CPI-pretreated patients
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